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Low-dose and very low-dose intravitreal bevacizumab (IVB) have been reported to be successful in short-term treatment of type 1 retinopathy of prematurity (ROP), down to an initial dose of 0.004 mg. We now report 12-month outcomes for these infants.Masked, multicenter, dose de-escalation study.One hundred twenty prematurely born infants with type 1 ROP.A cohort of 120 infants with type 1 ROP in at least 1 eye from 2 sequential dose de-escalation studies of low-dose IVB (0.25 mg, 0.125 mg, 0.063 mg, and 0.031 mg) or very low-dose IVB (0.016 mg, 0.008 mg, 0.004 mg, and 0.002 mg) to the study eye; the fellow eye (if also type 1) received 1 dose level higher of IVB. After primary success or failure at 4 weeks, clinical management was at investigator discretion, including all additional treatment.Reactivation of severe ROP by 6 months corrected age, additional treatments, retinal and other ocular structural outcomes, and refractive error at 12 months corrected age.Sixty-two of 113 study eyes (55%) and 55 of 98 fellow eyes (56%) received additional treatment. Of the study eyes, 31 (27%) received additional ROP treatment, and 31 (27%) received prophylactic laser therapy for persistent avascular retina. No trend toward a higher risk of additional ROP treatment related to initial IVB doses was found. However, time to reactivation among study eyes was shorter in eyes that received very low-dose IVB (mean, 76.4 days) than in those that received low-dose IVB (mean, 85.7 days). At 12 months, poor retinal outcomes and anterior segment abnormalities both were uncommon (3% and 5%, respectively), optic atrophy was noted in 10%, median refraction was mildly myopic (-0.31 diopter), and strabismus was present in 29% of infants.Retinal structural outcomes were very good after low- and very low-dose IVB as initial treatment for type 1 ROP, although many eyes received additional treatment. The rate of reactivation of severe ROP was not associated with dose; however, a post hoc data-driven analysis suggested that reactivation was sooner with very low doses.

Purpose To review the available evidence on the ocular safety and efficacy of anti-vascular endothelial growth factor (VEGF) agents for the treatment of retinopathy of prematurity (ROP) compared with laser photocoagulation therapy. Methods A literature search of the PubMed and Cochrane Library databases was conducted last on September 6, 2016, with no date restrictions and limited to articles published in English. This search yielded 311 citations, of which 37 were deemed clinically relevant for full-text review. Thirteen of these were selected for inclusion in this assessment. The panel methodologist assigned ratings to the selected articles according to the level of evidence. Results Of the 13 citations, 6 articles on 5 randomized clinical trials provided level II evidence supporting the use of anti-VEGF agents, either as monotherapy or in combination with laser therapy. The primary outcome for these articles included recurrence of ROP and the need for retreatment (3 articles), retinal structure (2 articles), and refractive outcome (1 article). Seven articles were comparative case series that provided level III evidence. The primary outcomes included the effects of anti-VEGF treatment on development of peripheral retinal vessels (1 article), refractive outcomes (1 article), or both structural and refractive or visual outcomes (5 articles). Conclusions Current level II and III evidence indicates that intravitreal anti-VEGF therapy is as effective as laser photocoagulation for achieving regression of acute ROP. Although there are distinct ocular advantages to anti-VEGF pharmacotherapy for some cases (such as eyes with zone I disease or aggressive posterior ROP), the disadvantages are that the ROP recurrence rate is higher, and vigilant and extended follow-up is needed because retinal vascularization is usually incomplete. After intravitreal injection, bevacizumab can be detected in serum within 1 day, and serum VEGF levels are suppressed for at least 8 to 12 weeks. The effects of lowering systemic VEGF levels on the developing organ systems of premature infants are unknown, and there are limited long-term data on potential systemic and neurodevelopmental effects after anti-VEGF use for ROP treatment. Anti-VEGF agents should be used judiciously and with awareness of the known and unknown or potential side effects.

Objective To assess the accuracy with which available retinopathy of prematurity (ROP) predictive models detect clinically significant ROP and to what extent and at what risk these models allow for the reduction of screening examinations for ROP. Methods A literature search of the PubMed and Cochrane Library databases was conducted last on May 1, 2015, and yielded 305 citations. After screening the abstracts of all 305 citations and reviewing the full text of 30 potentially eligible articles, the panel members determined that 22 met the inclusion criteria. One article included 2 studies, for a total of 23 studies reviewed. The panel extracted information about study design, study population, the screening algorithm tested, interventions, outcomes, and study quality. The methodologist divided the studies into 2 categories—model development and model validation—and assigned a level of evidence rating to each study. One study was rated level I evidence, 3 studies were rated level II evidence, and 19 studies were rated level III evidence. Results In some cohorts, some models would have allowed reductions in the number of infants screened for ROP without failing to identify infants requiring treatment. However, the small sample size and limited generalizability of the ROP predictive models included in this review preclude their widespread use to make all-or-none decisions about whether to screen individual infants for ROP. As an alternative, some studies proposed approaches to apply the models to reduce the number of examinations performed in low-risk infants. Conclusions Additional research is needed to optimize ROP predictive model development, validation, and application before such models can be used widely to reduce the burdensome number of ROP screening examinations.

Purpose Fetal mice require light exposure in utero during early gestation for normal vascular development in the eye. Because angiogenic abnormalities in retinopathy of prematurity (ROP) are manifested in preterm infants, we investigated whether day length during early gestation was associated with severe ROP (SROP). Design Single-center, retrospective cohort study. Participants We included a total of 343 premature infants (401-1250 g birth weight [BW], from 1998-2002): 684 eyes (1 eye each of 2 patients excluded) with 76 eyes developing SROP, defined as (1) classic threshold ROP in zone I or II, (2) type 1 ROP in zone I, or (3) in a few eyes, type 1 ROP in posterior zone II that was treated. Methods For each infant, average day length (ADL) was calculated during different cumulative time periods and time windows after the estimated date of conception (EDC). Multiple logistic regression analysis (with generalized estimating equations to account for inter-eye correlation) was performed. Main outcome measures Association of ADL during early gestation with SROP. Results In a model evaluating all 684 eyes with 76 eyes developing SROP, BW, gestational age, multiple births, race, per capita income in the mother's residence ZIP code, and ADL during the first 90 days after the EDC were factors associated with the development of SROP. Each additional hour of ADL (90 days) decreased the likelihood of SROP by 28% (P = 0.015; odds ratio [OR], 0.72; 95% confidence interval [CI], 0.55-0.94). In a model evaluating the subset of 146 prethreshold ROP eyes with 76 eyes developing SROP, each additional hour of ADL during the first 105 days after the EDC decreased the likelihood of SROP by 46% (P = 0.001; OR, 0.54; 95% CI, 0.37-0.78). Time windows when ADL was most closely associated with SROP were 31 to 60 days and 61 to 90 days after the EDC for the all eyes and the prethreshold ROP eyes models, respectively. Conclusions Higher ADL during early gestation was associated with a lower risk for SROP and may imply a role for prophylactic light treatment during early gestation to decrease the risk of SROP.

Objective To evaluate the severity of postoperative inflammation, degree of patient discomfort, adequacy of wound closure, and length of operating time when using fibrin glue compared with sutures to close limbal conjunctival incisions after strabismus surgery. Methods Literature searches of the PubMed and Cochrane Library databases were last conducted on January 24, 2013, and resulted in 24 citations, including 2 not in the English language. All citations were reviewed in full text. Five studies compared fibrin glue (68 eyes) with sutures (74 eyes) for closure of limbal conjunctival incisions in patients undergoing strabismus surgery and were included in this assessment; no studies were found that evaluated fornix incisions. A quality rating was assigned to each study using criteria specifically developed for this assessment. Results No level I studies were found, and 5 level II studies were identified. There was significantly less postoperative inflammation and patient discomfort for 1 to 3 weeks after strabismus surgery for eyes treated with fibrin glue compared with sutures. In 3 studies that evaluated wound apposition, 2 of 50 eyes (4%) with conjunctival incisions that were initially closed using fibrin glue subsequently developed a wound gap that required suture repair. In the 2 studies that compared surgical time, fibrin glue required 1 to 5 minutes less time than suturing in 1 study and 55% less time (3.8 vs. 8.4 minutes) in a second study. These 5 studies did not evaluate the cost-effectiveness or risk of viral transmission from fibrin glue. Conclusions Studies in the literature suggest that the off-label use of fibrin glue to close limbal conjunctival incisions in strabismus surgery resulted in less postoperative inflammation and required shorter operating time compared with sutures, but it increased the percentage of wounds requiring subsequent repair with sutures. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Objective To compare intraocular pressure (IOP) measurements in children 18 years of age and younger using rebound tonometry and applanation tonometry and the feasibility of using these techniques in children. Methods Literature searches of the PubMed and the Cochrane Library databases were last conducted in June 2012 and resulted in 43 citations, including citations not in English. Of these 43 citations, 4 studies met the inclusion criterion following full text review. A level of evidence rating was assigned to each study using criteria specifically developed for this assessment. Results No level I study was found in the literature search, and 2 level II and 2 level III studies were identified. Intraocular pressure was 2 to 3 mmHg higher using rebound tonometry compared with Goldmann applanation tonometry in the 2 level II studies performed in a clinic setting and in 1 level III study performed on children under general anesthesia. However, IOP was lower in 1 level III study in which noncontact applanation tonometry was compared with rebound tonometry. Bland-Altman plots showed that the difference in IOP for rebound versus Goldmann applanation tonometry increased as the IOP increased. The success rate for measuring IOP was markedly higher in children 3 years of age and younger using rebound tonometry compared with noncontact tonometry in 1 level III study. Conclusions Rebound tonometry seems to be a reasonably accurate instrument that allows the IOP to be measured in many children without using general anesthesia. More data are required to assess better how the differences between instruments vary with IOP measurement. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Objective To evaluate the accuracy of detecting clinically significant retinopathy of prematurity (ROP) using wide-angle digital retinal photography. Methods Literature searches of PubMed and the Cochrane Library databases were conducted last on December 7, 2010, and yielded 414 unique citations. The authors assessed these 414 citations and marked 82 that potentially met the inclusion criteria. These 82 studies were reviewed in full text; 28 studies met inclusion criteria. The authors extracted from these studies information about study design, interventions, outcomes, and study quality. After data abstraction, 18 were excluded for study deficiencies or because they were superseded by a more recent publication. The methodologist reviewed the remaining 10 studies and assigned ratings of evidence quality; 7 studies were rated level I evidence and 3 studies were rated level III evidence. Results There is level I evidence from ≥5 studies demonstrating that digital retinal photography has high accuracy for detection of clinically significant ROP. Level III studies have reported high accuracy, without any detectable complications, from real-world operational programs intended to detect clinically significant ROP through remote site interpretation of wide-angle retinal photographs. Conclusions Wide-angle digital retinal photography has the potential to complement standard ROP care. It may provide advantages through objective documentation of clinical examination findings, improved recognition of disease progression by comparing previous photographs, and the creation of image libraries for education and research. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Objective To evaluate the role of cryotherapy in the current treatment of retinopathy of prematurity (ROP). Methods Literature searches of PubMed and the Cochrane Library were conducted on December 2, 2009, for articles published after 1984. The searches included all languages and retrieved 187 relevant citations. Thirteen articles were deemed relevant to the assessment question and were rated according to the strength of evidence. Four articles reported results from 2 large multicenter randomized clinical trials, and the remaining 9 articles reported results of 3 small randomized trials that directly compared cryotherapy and laser. Results Neither of the multicenter randomized clinical trials was a direct comparison of cryotherapy with laser. These studies were used to evaluate the comparative trials based on treatment criteria, study populations, and clinical results. Higher percentages of poor structural and functional outcomes generally were seen in eyes treated with cryotherapy compared with eyes undergoing laser treatment. Higher rates of systemic complications and myopia also were identified after treatment with cryotherapy. Conclusions Despite a relative paucity of level I evidence directly comparing cryotherapy and laser treatment for threshold ROP, the literature suggests that neonatal facilities should gain access to laser technology and laser-trained ophthalmic staff to achieve better outcomes for treatment of the disease. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

To assess the accuracy with which available retinopathy of prematurity (ROP) predictive models detect clinically significant ROP and to what extent and at what risk these models allow for the reduction of screening examinations for ROP.A literature search of the PubMed and Cochrane Library databases was conducted last on May 1, 2015, and yielded 305 citations. After screening the abstracts of all 305 citations and reviewing the full text of 30 potentially eligible articles, the panel members determined that 22 met the inclusion criteria. One article included 2 studies, for a total of 23 studies reviewed. The panel extracted information about study design, study population, the screening algorithm tested, interventions, outcomes, and study quality. The methodologist divided the studies into 2 categories-model development and model validation-and assigned a level of evidence rating to each study. One study was rated level I evidence, 3 studies were rated level II evidence, and 19 studies were rated level III evidence.In some cohorts, some models would have allowed reductions in the number of infants screened for ROP without failing to identify infants requiring treatment. However, the small sample size and limited generalizability of the ROP predictive models included in this review preclude their widespread use to make all-or-none decisions about whether to screen individual infants for ROP. As an alternative, some studies proposed approaches to apply the models to reduce the number of examinations performed in low-risk infants.Additional research is needed to optimize ROP predictive model development, validation, and application before such models can be used widely to reduce the burdensome number of ROP screening examinations.

To evaluate the severity of postoperative inflammation, degree of patient discomfort, adequacy of wound closure, and length of operating time when using fibrin glue compared with sutures to close limbal conjunctival incisions after strabismus surgery.Literature searches of the PubMed and Cochrane Library databases were last conducted on January 24, 2013, and resulted in 24 citations, including 2 not in the English language. All citations were reviewed in full text. Five studies compared fibrin glue (68 eyes) with sutures (74 eyes) for closure of limbal conjunctival incisions in patients undergoing strabismus surgery and were included in this assessment; no studies were found that evaluated fornix incisions. A quality rating was assigned to each study using criteria specifically developed for this assessment.No level I studies were found, and 5 level II studies were identified. There was significantly less postoperative inflammation and patient discomfort for 1 to 3 weeks after strabismus surgery for eyes treated with fibrin glue compared with sutures. In 3 studies that evaluated wound apposition, 2 of 50 eyes (4%) with conjunctival incisions that were initially closed using fibrin glue subsequently developed a wound gap that required suture repair. In the 2 studies that compared surgical time, fibrin glue required 1 to 5 minutes less time than suturing in 1 study and 55% less time (3.8 vs. 8.4 minutes) in a second study. These 5 studies did not evaluate the cost-effectiveness or risk of viral transmission from fibrin glue.Studies in the literature suggest that the off-label use of fibrin glue to close limbal conjunctival incisions in strabismus surgery resulted in less postoperative inflammation and required shorter operating time compared with sutures, but it increased the percentage of wounds requiring subsequent repair with sutures.The author(s) have no proprietary or commercial interest in any materials discussed in this article.

To evaluate the role of cryotherapy in the current treatment of retinopathy of prematurity (ROP).Literature searches of PubMed and the Cochrane Library were conducted on December 2, 2009, for articles published after 1984. The searches included all languages and retrieved 187 relevant citations. Thirteen articles were deemed relevant to the assessment question and were rated according to the strength of evidence. Four articles reported results from 2 large multicenter randomized clinical trials, and the remaining 9 articles reported results of 3 small randomized trials that directly compared cryotherapy and laser.Neither of the multicenter randomized clinical trials was a direct comparison of cryotherapy with laser. These studies were used to evaluate the comparative trials based on treatment criteria, study populations, and clinical results. Higher percentages of poor structural and functional outcomes generally were seen in eyes treated with cryotherapy compared with eyes undergoing laser treatment. Higher rates of systemic complications and myopia also were identified after treatment with cryotherapy.Despite a relative paucity of level I evidence directly comparing cryotherapy and laser treatment for threshold ROP, the literature suggests that neonatal facilities should gain access to laser technology and laser-trained ophthalmic staff to achieve better outcomes for treatment of the disease.